Mezigdomide, Carfilzomib, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma in Patients With Extramedullary Disease

Exclusion Criteria

• •Participant has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, pomalidomide (including ≥ grade 3 rash during prior thalidomide, lenalidomide, or pomalidomide therapy), carfilzomib or dexamethasone, any cereblon E3 ligase modulators (CELMoD) agents, or the excipients contained in the formulations, or participant has any contraindications per local prescribing information
• •Administration of strong CYP3A modulators or proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) within 2 weeks of starting study intervention
• •Participant is unable or unwilling to undergo protocol required thromboembolism prophylaxis
• •Patient has evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
• •Any medical conditions that, in the investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participation in this study
• •Known active infection requiring parenteral or oral anti-infective treatment within the past 14 days
• •Participant has a history of prior malignancy other than MM, except if the participant has been free of disease for ≥ 3 years or the participant had 1 of the following noninvasive malignancies treated with curative intent without known recurrence:
• •* Basal or squamous cell carcinoma of the skin
• •* Carcinoma in situ of the cervix or breast
• •* Stage 1 bladder cancer
• •* Incidental histological findings of localized prostate cancer such as tumor stage 1a or 1b (T1a or T1b) using the tumor, nodes, and metastasis (TNM) classification of malignant tumors OR prostate cancer that has been treated with curative intent
• •Other ongoing anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to patient registration
• •Pregnant or breast-feeding females
• •Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
• •Known active HIV or hepatitis B or C viral infection
• •Known history of HIV infection
• •Systemic amyloidosis or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[M-protein\] and skin changes)
• •Prior peripheral stem cell transplant within 12 weeks of study enrollment
• •Radiotherapy within 14 days prior to cycle 1 day 1. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy
• •Known intolerance to steroid therapy
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, severe cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• •Carfilzomib-refractory in the most recent line of therapy
• •Prior treatment with mezigdomide
• •Contraindication against conscious sedation
• •Unwilling or unable to follow protocol requirements
• •Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug